Session Information
Date: Tuesday, October 23, 2018
Title: Systemic Sclerosis and Related Disorders – Clinical Poster III
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Immunosuppression is used to treat ILD, but little is known about its benefits in mild ILD or late SSc, as these patients were excluded from randomized trials. Our aim was to determine if, in SSc patients with incident ILD, the effectiveness of immunosuppression was differential according to ILD severity and SSc duration.
Methods: We studied all SSc patients with incident ILD, using data from the Canadian Scleroderma Research Group registry (> 98% met 2013 ACR/EULAR classification criteria for SSc). The primary exposure was time dependent ever/never exposure to methotrexate, cyclophosphamide, mycophenolate, azathioprine and/or cyclosporin A. The primary outcome was progression-free survival, with clinically meaningful progression defined as >10% decline in forced vital capacity (FVC), or >5% to <10% decline in FVC and >15% decline in diffusion capacity of lung for carbon monoxide (DLCO) (OMERACT CTD-ILD 2015). Using ILD diagnosis as time zero, time to progression or death was compared between exposed and unexposed subjects. A marginal structural Cox model with inverse probability of treatment weights and multiple imputation was used to account for potential confounding and for missing data, respectively. Weights were constructed using age at baseline, sex, race, disease subtype (diffuse vs limited), and autoantibodies. Mild ILD was defined as FVC >80% predicted, and late SSc duration was defined as >7 years since first non-Raynaud. Our final model also adjusted for age, sex, race, disease subtype, and autoantibodies. Interaction terms were examined to determine if immunosuppression effectiveness differed in mild vs moderate/severe ILD, or in late vs early SSc. Subjects were censored at the visit when the outcome (death or progression) was first recorded, lost to follow-up or at last study visit.
Results: There were 204 SSc patients with incident ILD; 67 were exposed to immunosuppression at time zero or during follow up and 134 remained unexposed throughout follow-up (Table 1). In our models, subjects exposed to immunosuppression tended to have a lower estimated risk of progression or death versus unexposed subjects: weighted hazard ratio (HR) 0.65 (95% CI 0.34, 1.25). We were unable to detect a differential effect of immunosuppression according to ILD severity or SSc duration (p=0.24 and p=0.85 for interaction terms, respectively).
Conclusion: We were unable to detect a differential effect of immunosuppression according to ILD severity or SSc duration; this may be due to lack of power. A larger sample would be required to resolve this uncertainty and answer the important clinical question of whether SSc patients perceived to be at increased risk of progressive ILD, even if mild or later in the disease course, benefit from immunosuppression.
Table 1. Baseline characteristics of the cohort, stratified by exposure status
|
|
Never-exposed to treatments (N=134) |
Ever-exposed to treatments (N=67) |
||
|
|
Mean (SD) or N (%) |
Missing (%) |
Mean (SD) or N (%) |
Missing (%) |
|
Age, years |
60.5 (10.7) |
– |
53.6 (12.6) |
– |
|
Female |
122 (89.1%) |
– |
56 (83.6%) |
– |
|
White |
97 (73.5%) |
4 |
44 (67.7%) |
3 |
|
Smoking (ever vs. never) |
75 (59.1%) |
7 |
39 (63.9%) |
9 |
|
Disease duration from 1st non-RP |
14.2 (10.0) |
– |
9.2 (7.8) |
– |
|
Diffuse subtype (vs. limited) |
62 (45.3%) |
– |
49 (73.1%) |
– |
|
Modified Rodnan skin score (0-51) |
9.5 (8.5) |
2 |
13.8 (11.4) |
1 |
|
Anti-centromere |
50 (39.7%) |
8 |
10 (15.6%) |
4 |
|
Anti-topoisomerase 1 |
20 (15.9%) |
8 |
15 (23.4%) |
4 |
|
Anti-RNA polymerase III |
19 (15.1%) |
8 |
18 (28.1%) |
4 |
|
Anti-Ro52/TRIM21 |
35 (27.8%) |
8 |
14 (21.9%) |
4 |
|
FVC, % predicted |
90.8 (17.4) |
16 |
84.8 (17.8) |
19 |
|
TLC, % predicted |
95.5 (16.6) |
23 |
88.9 (14.4) |
28 |
|
DLCO, % predicted |
65.5 (19.4) |
23 |
63.9 (22.8) |
31 |
To cite this abstract in AMA style:
Hoa S, Bernatsky S, Steele R, Hudson M. Is Effectiveness of Immunosuppression for Interstitial Lung Disease in Systemic Sclerosis (SSc) Modified By Lung Disease Severity or SSc Duration? [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/is-effectiveness-of-immunosuppression-for-interstitial-lung-disease-in-systemic-sclerosis-ssc-modified-by-lung-disease-severity-or-ssc-duration/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-effectiveness-of-immunosuppression-for-interstitial-lung-disease-in-systemic-sclerosis-ssc-modified-by-lung-disease-severity-or-ssc-duration/